Summary To address the significant burden of HIV-infected mothers and children in India, the National AIDS Control Organization (NACO) and Maharashtra State AIDS Control Society (MSACS) are preparing to implement the 2010 revised World Health Organization (WHO) prevention of mother-to-child HIV transmission (PMTCT) guidelines in April 2012. This updated PMTCT program in India has four major components: 1) Provision of antiretroviral treatment (ART) to all HIV-infected pregnant women and breastfeeding mothers; 2) Promotion of exclusive breastfeeding for 6 months; 3) Administration of six weeks extended nevirapine prophylaxis (SWEN) to all HIV-exposed infants and 4) Engagement and retention of women and infants in postpartum HIV care to facilitate early infant diagnosis. The overall goal of our study is to evaluate a strategic, integrated and innovative approach to improve the capacity of outreach workers (ORWs) visiting patients in their homes, to support uptake of PMTCT services. Our intervention, based on an innovative adaptation of an situated information-motivation-behavioral skills model of care initiation and maintenance (sIMB-CIM), is called COMmunity home Based INDia PMTCT (COMBIND PMTCT) study and has the following four strategies: 1) Specialized ORW training that includes assessments of knowledge retention and provides targeted re-training; 2) Strategic feedback to ORWs, to improve their performance; 3) Targeted feedback to mothers to enhance uptake of the 4 specific services; and 4) Use of an open-source, award-winning mobile health (mHealth) platform (eMOCHA) that facilitates communication with ORWs and patients, provides strategic feedback to the providers, patients and program, and optimizes uptake of the 4 key PMTCT components. The central hypothesis is that intervention proposed will result in optimized program implementation in each of the 4 key PMTCT components. The specific aims of the COMBIND study are: 1) To examine the impact of COMBIND PMTCT on uptake of the four major components of NACO's PMTCT program, using a cluster randomized trial design in four high-HIV burden districts of Maharashtra ; 2) Conduct a mixed-methods evaluation of the intervention to assess the impacts and acceptability of the proposed targeted feedback system for both ORWs and women and use and feasibility of the mHealth platform. Our study has a high likelihood of success because our collaborative, interdisciplinary, inter-institution Indo-US research team include Lakshya, a non-governmental organization (NGO) whose team members have several years of experience in clinical and implementation science projects; MSACS, a division of the Ministry of Health that provides leadership to HIV/AIDS program in Maharashtra State; and Johns Hopkins University, that has existing Indo-US collaboration with Lakshya and BJ Medical College, Pune, India and has extensive experience in collaborative research in clinical and implementation science projects.